Recent epidemiologic studies have reported a statistically significant association between short-term increases in airborne particulate matter and increased mortality and morbidity from respiratory and cardiovascular disease. Although many toxic effects of airborne particulate matter and many of its constituents have been demonstrated with a variety of animal models and, to a more limited extent, with human subjects, the mechanism(s) that would explain the reported associations at much lower concentrations remains to be elucidated. Given the results of the epidemiology studies and some of the toxicology data, this mechanism(s) probably involves premature death of health-compromised individuals who are already near death, increased susceptibility to infections, and exacerbation of pre-existing cardiovascular and pulmonary chronic diseases. Consistent with these observations, the purpose of this study is test the hypothesis that airborne particles act through interaction with th alveolar macrophage (AM) to cause an inflammatory response leading to increased pulmonary and cardiovascular stress that contributes to the increased morbidity and mortality observed in otherwise health- compromised individuals. This study will test whether airborne particulate matter causes apoptosis of human AM and/or change the macrophage phenotype that could result in lung inflammation. Preliminary results have demonstrated that other inflammatory particulates such as asbestos and silica induce apoptosis of human AM and appear to induce phenotypic changes in AM. The first specific aim will characterize whether airborne particles cause apoptosis of human AM. Particulate-induced human AM apoptosis (dose, role of particulate size and time) will be evaluated using morphology and DNA fragmentation by the TUNEL assay, Cell Death ELISA and DNA gel electrophoresis. The second specific aim will characterize whether airborne particles induce phenotypic changes in human AM that would cause a shift to a more inflammatory state in the lung. Human AM will be evaluated using two sets of surface markers (RFD1 and 7, and CD80 and CD86) to discriminate inflammatory versus suppressor human AM. The results from this work will be useful for developing strategies for subsequent mechanistic studies and improved evaluation of the potential risks of different airborne particles on human health.